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QuadW Foundation-AACR Fellowship for Clinical/Translational Sarcoma Research

The QuadW Foundation‐AACR Fellowship for Clinical/Translational Sarcoma Research represents a joint effort to encourage and support a postdoctoral or clinical research fellow to work on mentored sarcoma research and to establish a successful career path in this field. Eligibility is limited to postdoctoral and clinical research fellows within the first five years of their fellowship. The research proposed for funding may be translational or clinical in nature and must have direct applicability and relevance to sarcoma research. 

2018 Grantee

Lillian M. Guenther, PhDLillian M. Guenther, MD
Clinical Fellow
Dana-Farber Cancer Institute
Boston, Massachusetts
headshot_1 line spacerNovel Drug Combinations with CDK4/6 Inhibitors in Ewing Sarcoma

Scientific Statement of Research
Ewing sarcoma, an aggressive small round blue cell tumor of childhood, is a frequent cause of pediatric cancer deaths despite multi-modal therapies. Recent efforts to identify disease-specific dependency genes through CRISPR-Cas9 and RNAi technologies have revealed CDK4 as a critical Ewing sarcoma dependency. CDK4/6 inhibitors have had successes in several adult malignancies and there is good pediatric safety data for this drug class. However, rational combination therapies are needed to achieve maximal patient benefit. Dr. Guenther aims to investigate synergistic targets with CDK4 utilizing a genome-scale CRISPR-Cas9 synergy screening technique in Ewing sarcoma cell lines. Focusing on druggable hits, she will then validate synergistic combinations emerging from this effort both in vitro in established cell lines and in vivo using patient-derived xenograft models. The goal of these studies is to produce comprehensive preclinical validation of multiple novel drug combinations that can be rapidly moved into trials for Ewing sarcoma patients.

Biography
Dr. Lillian (Lily) Guenther received her BA degree from Brown University in 2005 and her MD degree from the State University of New York Downstate Medical Center College of Medicine in 2011. Dr. Guenther completed her general pediatrics residency in the Boston Combined Residency Program in 2014 and her fellowship in Pediatric Hematology/Oncology at Dana-Farber Cancer Institute and Boston Children’s Hospital in 2017. She joined the laboratory of Dr. Kimberly Stegmaier in 2015. As a post-doctoral fellow, Dr. Guenther studies novel genomic dependencies in Ewing sarcoma and osteosarcoma with the goal of transforming therapeutic options for patients with these diseases.

Acknowledgement of Support
The QuadW Foundation-AACR Fellowship for Clinical/Translational Sarcoma Research provides a crucial rung of support for me as an early career pediatric oncology physician-scientist. This fellowship will protect my time to perform innovative research, allowing me to launch my career as a laboratory-based translational sarcoma researcher and a pediatric oncology clinician.

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2017 Grantee

Wagner_90x110.jpg

Michael J. Wagner, MD
Oncology Fellow
University of Texas MD Anderson Cancer Center
Houston, Texas
Overcoming primary resistance to VEGF/VEGFR targeted agents in headshot_1 line spacerangiosarcoma

Scientific Statement of Research
Malignancies arising from endothelial cells such as angiosarcomas are rare; however, the tumors that do arise tend to be highly aggressive and difficult to treat. While high grade endothelial malignancies respond well to traditional chemotherapy, their durability is poor and the tumors acquire drug resistance rapidly. Targeted therapies such as anti-angiogenic agents that would be intuitive for these malignancies have had limited success in the clinic. One reason for the limited therapeutic activity of targeted drugs in angiosarcoma is the presence of oncogenic mutations. Dr. Wagner is investigating the role of somatic mutations in PLCG1 and PTPRB in angiosarcoma. He will test the hypothesis that these mutations lead to activation of the MAPK pathway, and that treatment aimed at MEK and VEGFR2 targets both angiosarcoma cells and host endothelial cells in the tumor microenvironment to inhibit tumor growth. These data will represent the first investigation of the potential for tailoring treatment decisions based on somatic mutations in angiosarcoma.

Biography
Dr. Michael Wagner is a medical oncology fellow at MD Anderson Cancer Center. He received his MD from Harvard Medical School in Boston and completed an internal medicine residency at Mount Sinai Hospital in New York. He is conducting translational research aimed at improving outcomes for patients with sarcoma, with a focus on understanding the molecular drivers of angiosarcoma.

Acknowledgement of Support
The QuadW Foundation-AACR Fellowship will further my goal to pursue hypothesis-driven research with direct implications for patient care. Leading an in-depth translational research project such as the project funded by this grant will strengthen my ability to design ground breaking experiments and to conduct meaningful translational research as I begin my career as a sarcoma clinician and researcher.

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